The role of chelatable zinc in microglial activation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10307
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kochi University
• Principal Investigator: Higashi Youichirou 高知大学, 教育研究部医療学系基礎医学部門, 助教 (80380062)
• Co-Investigator(Kenkyū-buntansha): 上羽 哲也 高知大学, 教育研究部医療学系臨床医学部門, 教授 (00314203) ; 齊藤 源顕 高知大学, 教育研究部医療学系基礎医学部門, 教授 (60273893)
• Co-Investigator(Renkei-kenkyūsha): YAWATA Toshio 高知大学, 教育研究部医療学系臨床医学部門, 助教 (40380323) ; SHIMIZU Shogo 高知大学, 教育研究部医療学系基礎医学部門, 助教 (90721853)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ミクログリア / 脳卒中後遺症 / キレータブル亜鉛

Outline of Final Research Achievements

Here, we examined the role of extracellular zinc in microglial M1 activation. Pretreatment with ZnCl2 caused aggravation of pro-inflammatory cytokine secretions when M1 activation was induced by lipopolysaccharide. The intracellular zinc chelator, the radical scavenger, and the P2X7R antagonist suppressed the effects of zinc pre-treatment on microglia. Furthermore, ischemia-reperfusion induced endogenous zinc release, resulting in up-regulation of pro-inflammatory cytokine, and the M1 marker, in addition to cognitive impairments, all of which were suppressed by the zinc chelator. Extracellular zinc may prime microglia to enhance the production of pro-inflammatory cytokines through P2X7R activation followed by ROS generation in response to M1 stimuli, which may cause cognitive impairments.

Free Research Field

神経薬理学